Journal Article
Diabetes Care, vol. 42, iss. 2, pp. 258-264, 2018
Authors
Emily K. Sims, Henry T. Bahnson, Julius Nyalwidhe, Leena Haataja, Asa K. Davis, Cate Speake, Linda A. DiMeglio, Janice Blum, Margaret A. Morris, Raghavendra G. Mirmira, Jerry Nadler, Teresa L. Mastracci, Santica Marcovina, Wei-Jun Qian, Lian Yi, Adam C. Swensen, Michele Yip-Schneider, C. Max Schmidt, Robert V. Considine, Peter Arvan, Carla J. Greenbaum, Carmella Evans-Molina, Steven Willi, Tammy Calvano, Georgeanna Klingensmith, Heidi Haro, Ruth Weinstock, Suzan Bzdick, Robin Goland, Ellen Greenberg, Joyce Lee, Ashley Eason, Linda DiMeglio, Stephanie Woerner, Andrew Ahmann, Rebecca Fitch, Kathleen Bethin, Michelle Ecker, Irl Hirsch, Christina Peterson, David Liljenquist, Brandon Robison, Richard Bergenstal, Beth Olson, Eda Cengiz, Amy Steffen, Anne Peters, Perez Hinton, Janet McGill, Lori Buechler, Eva Tsalikian, Joanne Cabbage, Mark Clements, Lois Hester, Davida Kruger, Heather Remtema, Desmond Schatz, Jamie Thomas, William Zipf, Diane Seiple, Henry Rodriguez, Danielle Henson, Jill Simmons, Faith Brendle, Brandon Nathan, Kara Schmid, Kathleen Arnold, Sharon Sellers, David Harlan, Lisa Hubacz, John Buse, Julie Tricome, Michael Rickels, Cornelia Dalton-Bakes, Leroy Schroeder, Amanda Roark, Amy Potter, Faith Brendle,
Abstract
OBJECTIVE
Abnormally elevated proinsulin secretion has been reported in type 2 and early type 1 diabetes when significant C-peptide is present. We questioned whether individuals with long-standing type 1 diabetes and low or absent C-peptide secretory capacity retained the ability to make proinsulin.
RESEARCH DESIGN AND METHODS
C-peptide and proinsulin were measured in fasting and stimulated sera from 319 subjects with long-standing type 1 diabetes (≥3 years) and 12 control subjects without diabetes. We considered three categories of stimulated C-peptide: 1) C-peptide positive, with high stimulated values ≥0.2 nmol/L; 2) C-peptide positive, with low stimulated values ≥0.017 but <0.2 nmol/L; and 3) C-peptide <0.017 nmol/L. Longitudinal samples were analyzed from C-peptide–positive subjects with diabetes after 1, 2, and 4 years.
RESULTS
Of individuals with long-standing type 1 diabetes, 95.9% had detectable serum proinsulin (>3.1 pmol/L), while 89.9% of participants with stimulated C-peptide values below the limit of detection (<0.017 nmol/L; n = 99) had measurable proinsulin. Proinsulin levels remained stable over 4 years of follow-up, while C-peptide decreased slowly during longitudinal analysis. Correlations between proinsulin with C-peptide and mixed-meal stimulation of proinsulin were found only in subjects with high stimulated C-peptide values (≥0.2 nmol/L). Specifically, increases in proinsulin with mixed-meal stimulation were present only in the group with high stimulated C-peptide values, with no increases observed among subjects with low or undetectable (<0.017 nmol/L) residual C-peptide.
CONCLUSIONS
In individuals with long-duration type 1 diabetes, the ability to secrete proinsulin persists, even in those with undetectable serum C-peptide.
